Welcome to the CMC Strategy Forum We are pleased to welcome you to the CMC Strategy Forum. The purpose of the CMC Strategy Forum is to provide a venue for biotechnology/biological product discussion. The meetings focus on relevant CMC issues throughout the lifecycle of a product and thereby foster collaborative technical and regulatory interactions. The Forum strives to share information with the regulatory agencies to assist them in merging good scientific and regulatory practices. Outcomes of the Forum meetings are published in an appropriate peer-reviewed journal. Each meeting will focus on a CMC related issue such as product characterization, comparability, specifications, etc. The format of each meeting will consist of case studies and presentations by Industry and/or FDA experts to introduce the topic and the key issues of concern. Breakout sessions will then be conducted to allow for additional discussion on the technical and regulatory details of the topics. It is envisioned that the final outcome of the workshop discussions will be the development of a document to be submitted to the appropriate Regulatory Agency designees for their consideration in developing and/or clarifying good regulatory practice guidelines for biotechnology derived products. The success of the CMC Strategy Forum will depend on your active participation in discussing and raising issues pertaining to development of biologics. We encourage you to participate wholeheartedly in the workshops that have been designed to stimulate exchange of ideas and information. We would like to thank the speakers who are giving generously of their time and resources, and to you, for your attendance. We acknowledge the generosity of our program partners: AbbVie, Inc., Amgen Inc., Biogen, Eli Lilly and Company, F. Hoffmann-La Roche Ltd., Genentech, a Member of the Roche Group, Janssen Pharmaceutical R&D, LLC, MedImmune, A member of the AstraZeneca Group, Merck & Co., Inc., National Institute of Standards and Technology (NIST), Novo Nordisk A/S and Pfizer Inc. We are grateful for the expert management from CASSS and the audio-visual expertise of Michael Johnstone from MJ Audio-Visual Productions. Their experience and guidance in the preparation of this Forum has been invaluable.

ACKNOWLEDGEMENTS

CMC STRATEGY FORUM NORTH AMERICA PROGRAM COMMITTEE Siddharth Advant, Kemwell Biopharma Yves Aubin, Health Canada John Bishop, CBER, FDA Barry Cherney, Amgen Inc. JR Dobbins, Eli Lilly and Company Julia Edwards, Biogen Sarah Kennett, CDER, FDA Joseph Kutza, MedImmune, A member of the AstraZeneca Group Kimberly May, Merck & Co., Inc. Anthony Mire-Sluis, Amgen Inc. Stefanie Pluschkell, Pfizer, Inc. Nadine Ritter, Global Biotech Experts, LLC Reb Russell, Bristol-Myers Squibb Company Dieter Schmalzing, Genentech, a Member of the Roche Group Timothy Schofield, MedImmune, A member of the AstraZeneca Group Zahra Shahrokh, ZDev Consulting Jeffrey Staecker, BioPhia Consulting, Inc. Andrew Weiskopf, Biogen CMC STRATEGY FORUM GLOBAL STEERING COMMITTEE Siddharth Advant, KemWell Biopharma, USA John Dougherty, Eli Lilly and Company, USA Steven Kozlowski, CDER, FDA, USA Junichi Koga, Daiichi Sankyo Co., Ltd., Japan Rohin Mhatre, Biogen, USA Anthony Mire-Sluis, Amgen Inc., USA Marcelo Moreira, ANVISA-Brasilian National Health Surveillance Agency, Brasil Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland (Chair) Ilona Reischl, AGES-Austrian Medicines and Medical Devices Agency, Austria Anthony Ridgway, Health Canada, Canada Nadine Ritter, Global Biotech Experts, LLC, USA Daisaku Sato, PMDA-Pharmaceutical and Medical Devices Agency, Japan Thomas Schreitmüller, F. Hoffmann-La Roche Ltd., Switzerland Mark Schenerman, MedImmune, A member of the AstraZeneca Group, USA Karin Sewerin, BioTech Development AB, Sweden

The Organizing Committee gratefully acknowledges the pharmaceutical and biotechnology industry for their generous support

of the CMC Strategy Forum North America series:

SUSTAINING DIAMOND PROGRAM PARTNER

Genentech, a Member of the Roche Group F. Hoffmann-La Roche Ltd.

SUSTAINING PLATINUM PROGRAM PARTNER

AbbVie, Inc. Biogen

MedImmune, A member of the AstraZeneca Group

SUSTAINING GOLD PROGRAM PARTNER

Novo Nordisk A/S SUSTAINING SILVER PROGRAM PARTNER

Merck & Co., Inc. Pfizer, Inc.

PROGRAM PARTNERS

Amgen Inc. Eli Lilly and Company

Janssen Pharmaceutical R & D, LLC National Institute of Standards and Technology

(NIST)

The Scientific Organizing Committee gratefully acknowledges the following media for their promotional consideration of CMC Strategy

Forum North America January 2016:

LEADING MEDIA PARTNERS

BioProcess International International Pharmaceutical Quality

MEDIA PARTNERS

American Laboratory / LabCompare American Pharmaceutical Review

The Analytical Scientist BioProcessing Journal

Genetic Engineering & Biotechnology News Green Chemistry

LCGC North America The Medicine Maker

The Pathologist Pharmaceutical Outsourcing

separationsNOW.com Technology Networks

Forum Abstract Change Happens: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management FORUM CO-CHAIRS: Julia Edwards, Biogen, USA Joseph Kutza, MedImmune, A member of the AstraZeneca Group, USA Emanuela Lacana, CDER, FDA, USA Ingrid Markovic, CBER, FDA, USA SCIENTIFIC ORGANIZING COMMITTEE: Yves Aubin, Health Canada, Canada Michelle Frazier, AbbVie, Inc., USA Markus Goese, F. Hoffmann-La Roche Ltd., Switzerland Frank Montgomery, AstraZeneca, United Kingdom In the current global regulatory environment, the management of post-approval CMC changes is often unpredictable and inefficient. Timelines for change approval can vary, from months to years, depending on regional regulatory timelines. Therefore, in post-approval lifecycle management, the challenge is to maintain a constant supply of high quality product while supporting innovation and continual improvement. The purpose of this forum is to explore pathways for operational flexibility in the post-approval phase of the product lifecycle. Case studies will be illustrated with specific examples that leverage ICH Q8, Q9, Q10, and Q11 concepts, which drive toward globally consistent management of post-approval changes. In close alignment with ongoing work on ICH Q12, the forum will highlight the benefits of clearly defining established conditions (i.e., regulatory commitments), further reliance of Pharmaceutical Quality System (PQS), post-approval change management protocols, and the level of detail provided to support a change that ensures sufficient manufacturing flexibility. The questions this CMC Strategy Forum will answer:

1. What current or future regulatory pathways or tools would provide global operational flexibility in making post-approval changes? Does this look different for accelerated programs?

2. What are the benefits, challenges, and tradeoffs associated with leveraging these pathways and tools?

3. How do we close the gap between approval timelines (and data requirements) for post-licensure changes between ICH and non-ICH countries?

CMC Strategy Forum Program Summary

Change Happens: Technical and Regulatory Considerations for Pharmaceutical Product Lifecycle Management

Monday, January 25, 2016

07:30 – 17:00 Registration in the Senate Room 07:30 – 08:30 Breakfast in the Palm Court Ballroom 08:30 – 08:45 CASSS Welcome and Introductory Comments in the Grand Ballroom Wassim Nashabeh, F. Hoffmann-La Roche Ltd.

CMC Strategy Forum Welcome and Introductory Comments in the Grand Ballroom Julia Edwards, Biogen Joseph Kutza, MedImmune, A member of the AstraZeneca Group

Changing How We Make Change: ICH Q12 Global Status and Impact

Workshop Session One in the Grand Ballroom Session Chairs: Markus Goese, F. Hoffmann-La Roche Ltd. and Emanuela Lacana, CDER, FDA

08:45 – 09:15 FDA Perspectives on Established Conditions and ICH Q12 Ashley Boam, CDER, FDA, Silver Spring, MD USA 09:15 – 09:45 Regulatory Guidance for Product Lifecycle Management: Harmonization

Goals, Opportunities and Challenges Anthony Ridgway, Health Canada, Ottawa, ON Canada 09:45 – 10:15 Will ICH Q12 Truly Go Beyond Q8/11? Opportunities and Challenges

Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Basel, Switzerland 10:15 – 10:45 Networking Break in the Palm Court Ballroom 10:45 – 12:00 PANEL DISCUSSION – Questions and Answers Ashley Boam, CDER, FDA, USA

Daniela Marreco Cerqueira, ANVISA-Brasilian National Health Surveillance Agency, Brasil Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Ingrid Markovic, CBER, FDA, USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland

Peter Richardson, European Medicines Agency (EMA), United Kingdom Anthony Ridgway, Health Canada, Canada

12:00 – 13:30 Networking Lunch in the Palm Court Ballroom

Monday, January 25 continued…

Changing Lifecycle Management in Practice: The Reality of ICH Q12 Concepts Workshop Session Two in the Grand Ballroom

Session Chairs: Michelle Frazier, AbbVie, Inc. and Joseph Kutza, MedImmune, A member of the AstraZeneca Group

13:30 – 13:55 An Industry Perspective: The Complexity of Post-approval CMC Changes

and Proposed Regulatory Strategies Suzanne Murray, Biogen (representing Biophorum Operations Group (BPOG, United Kingdom)

13:55 – 14:20 Complexities of CMC Change Management & Q12 Opportunities

Jason Hampson, Amgen Inc., Thousand Oaks, CA USA 14:20 – 14:45 Improving Post-approval Change Processes as a Way to Ensure Technical

Innovation and Drug Product Availability Anders Vinther, Sanofi Pasteur, Swiftwater, PA USA 14:45 – 15:15 Networking Break in the Palm Court Ballroom 15:15 – 15:40 Managing the Product Lifecycle Continuum through Post-approval Change

Management Plans: An Industry Perspective Gresham Weatherly, AbbVie, Inc., North Chicago, IL USA 15:45 – 17:00 PANEL DISCUSSION – Questions and Answers

Jason Hampson, Amgen Inc., USA Kowid Ho, F. Hoffmann-La Roche Ltd., Switzerland

Suzanne Murray, Biogen (representing Biophorum Operations Group (BPOG, United Kingdom)

Anders Vinther, Sanofi Pasteur, USA Gresham Weatherly, AbbVie, Inc., USA 17:00 – 17:30 Recap of Program Summary Slide Presentation Demetra Macheras, AbbVie, Inc. Kimberly Wolfram, Biogen 17:30 – 17:45 Invitation to CMC Strategy Forum July 2016 18:00 – 19:15 Networking Reception in the Chinese Room

Changing How We Make Change: ICH Q12 Global Status and Impact

Session Chairs: Markus Goese, F. Hoffmann-La Roche Ltd. and Emanuela Lacana, CDER, FDA This session will provide an overview of the status of ICH Q12 from the perspective of both global regulators and industry. The opportunities and challenges will be shared from a several point’s vantage points. Further, the linkage between regional advancements in lifecycle management such as FDA's new draft guideline on established conditions and the broader global harmonization effort will be elucidated. NOTES:

Short Bio’s

Ashley Boam CDER, FDA Ashley Boam currently serves as acting director of the Office of Policy for Pharmaceutical Quality (OPPQ) in the Office of Pharmaceutical Quality (OPQ) in the Center for Drug Evaluation and Research (CDER). OPPQ is responsible for developing and clearly communicating science, and risk-based policies and standards related to drug product quality, including application review and inspection. This Office also coordinates OPQ’s work with international regulatory authorities on quality issues, leads CDER’s compendial operations, coordinates CDER’s involvement in quality standard-setting organizations, and addresses policy issues related to drug-device combination products. Prior to joining CDER, Ashley spent nearly 20 years in the Office of Device Evaluation (ODE) in FDA’s Center for Devices and Radiological Health (CDRH), serving as a scientific reviewer, a branch chief in the Division of Cardiology Devices, and finally as associate director for regulations and guidance for ODE. Ashley received her MSBE from the University of Alabama at Birmingham and her BSE from Tulane University, both in biomedical engineering. Daniela Marreco Cerqueira ANVISA-Brasilian National Health Surveillance Agency Graduated in biological sciences from the University of Brasilia (2002), degree in biological sciences (molecular biology) from the University of Brasilia (2003) and a PhD in biological sciences (molecular biology) from the University of Brasilia (2007). Activities practiced as a biologist until her entry into public career by tender in 2006. She is currently server of the Brazilian Health Surveillance Agency (ANVISA), with the post of the manager of the biological´s office at ANVISA. Specialized in Sanitary Vigilance by FIOCRUZ in 2010. Yasuhiro Kishioka Pharmaceuticals and Medical Devices Agency (PMDA) Dr. Kishioka is a principal reviewer in the Office of Cellular and Tissue-based Products of the Japanese regulatory agency, Pharmaceuticals and Medical Devices Agency (PMDA). Since joining PMDA in 2008, his main work is the pharmaceutical quality review of biotechnological/biological products. His areas of expertise also include biosimilars and he has been assigned as the ICH Q12 topic leader of Japanese regulatory authorities. He holds a PhD from Hokkaido University in meat science with emphasis in molecular biology.

Short Bio’s continued

Ingrid Markovic CDER, FDA Dr. Ingrid Markovic currently serves as a special advisor to the associate director for review management in the Office of the Center Director at Center for Biologics, U.S. FDA, where she is responsible for developing center-wide CMC Regulatory Review Policy and communication with external parties. Prior to her current position, Dr. Markovic served as an expert review scientist in the Office of Biotechnology Products at Center for Drugs, U.S. FDA. During her tenure at the FDA, Ingrid was also involved in developing Regulatory Review Policy for extractables & leachables, primary review of CMC sections for biotech/biologic products and biosimilars, participating in agency-wide regulatory guidance documents, pre-approval and surveillance inspections and co-chairing the new reviewer training program. Dr. Markovic trained in biochemistry, virology and natural products chemistry and has (co)-authored numerous peer-reviewed articles in these areas. She received her PhD degree from University of Wisconsin-Madison and her post-doctoral training was completed at the U.S. National Institutes of Health, NICHD in the laboratory of cellular and molecular biophysics. Wassim Nashabeh F. Hoffmann-La Roche Ltd. Dr. Wassim Nashabeh received his PhD in analytical chemistry from Oklahoma State University in 1993, and his post-doctoral fellowship in bioanaytical chemistry from The Barnett Institute at Northeastern University. Following a two-year research appointment at PerSeptive Biosystems, Wassim joined Genentech (A member of the Roche Group) in 1996 as a scientist and has since held several positions of increasing responsibilities including associate director of the methods validation group, director quality control, director in the CMC regulatory affairs group, senior director of CMC policy & strategy, global head of technical regulatory policy for the Roche Pharma Medicines Group and most recently as the global head of policy and international operations in PTR. His current responsibilities include development and advocacy of Roche key external positions and policies with global health authorities, industry associations and scientific organizations, as well as management of Roche technical regulatory international operations. Peter Richardson European Medicines Agency (EMA) Dr. Richardson is a pharmacist with a PhD in pharmaceutics from The Queens University, Belfast. He worked for a number of years (1991-98) in the pharmaceutical industry in the UK and Italy in the area of formulation research and development with focus on drug delivery, for companies such as Bristol-Myers Squibb, SmithKline Beecham, Pfizer and Serono. He joined the UK MHRA in 1998 as a pharmaceutical assessor, with time assessing chemical and abridged applications and with wide ranging experience of biotechnology/biological applications. He was the UK delegate for the CHMP Biologics Working Party prior to joining the European Medicines Agency in 2004, where he had roles as scientific administrator and head of biologicals in the quality of medicines sector. Since 2013, following restructuring of the Agency, he has held the role of head of quality office, a role which maintains oversight of the many aspects relating to quality of chemical and biological medicinal products.

Short Bio’s continued

Anthony Ridgway Health Canada Dr. Ridgway completed his PhD at McGill University in Montreal, and then proceeded to post-doctoral studies followed by an assistant professorship in the Cancer Research Laboratory and Department of Microbiology and Immunology at the University of Western Ontario. Academic research activities included work on the structure and expression of oncogenes, retroviral and HIV regulatory elements and inducible expression vectors. He has been with Health Canada since 1991 and in 1999, became manager of the biotherapeutics division, with responsibility for regulation of a wide range of products. In 2004, he guided the separation of his former division into three new divisions and became the senior regulatory scientist in the office of the director in the newly formed Centre for Evaluation of Radiopharmaceuticals and Biotherapeutics, BGTD. He holds a range of advisory and supervisory responsibilities that includes retaining managerial responsibility for the evaluation of product quality for radiopharmaceuticals and gene therapy products. He has been active with the ICH* since 1993, serving on Expert Working Groups addressing the quality of biotechnology products and is currently with Q12. He has been active on consecutive US Pharmacopoeia Committees of Experts, since June 2000. Dr. Ridgway has been extensively involved in the Canadian approach to subsequent-entry biologics (biosimilars), and the drafting and dissemination of Canadian guidance. *International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use

Presenter’s Abstracts

TBD Ashley Boam CDER, FDA, Silver Spring, MD USA Abstract was not available at the time of printing. Slides were not available at the time of printing. NOTES:

NOTES:

Regulatory Guidance for Product Lifecycle Management: Harmonization Goals, Opportunities and Challenges Anthony Ridgway Health Canada, Ottawa, ON Canada A perspective will be provided on the aspirations, issues, challenges and opportunities associated with development of the ICH Q12 guideline. Elements will include: the enduring value of risk-rationalized categorization of manufacturing changes requiring communication with the regulator; “Regulatory Commitments” or “Established Conditions” and their potential for leveraging “regulatory relief”; a possible new life for Post-Approval Change Management Protocols; and the potential for Q12 to have significant value beyond current ICH jurisdictions through “ICH-independent” harmonization and regulatory convergence. NOTES:

Will ICH Q12 Truly Go Beyond Q8/11? Opportunities and Challenges Wassim Nashabeh F. Hoffmann-La Roche Ltd., Basel, Switzerland This presentation will focus on the current challenges and opportunities facing the development of ICH Q12, the first ICH Q document solely focused on post-approval changes for pharmaceuticals. Q12 is seen as a continuation of the ICH Quality vision that started with Q8 continuing through Q11. Q12 can potentially holds the promise of bringing meaningful and pragmatic benefits following implementation, something that have not yet been truly realized yet through implementation of Q8/11, so that the original promise of the ICH Quality vision can be realized. The newly introduced concept of established conditions will be discussed from a pragmatic perspective including examples of how such conditions could be selected for a biologic, and be linked to knowledge and risk calibration. Slides were not available at the time of printing. NOTES:

NOTES:

Changing How We Make Change: ICH Q12 Global Status and Impact

Workshop Session One Panel Discussion – Questions and Answers Ashley Boam, CDER, FDA, USA Daniela Marreco Cerqueira, ANVISA-Brasilian National Health Surveillance Agency, Brasil Yasuhiro Kishioka, Pharmaceuticals and Medical Devices Agency (PMDA), Japan Ingrid Markovic, CBER, FDA, USA Wassim Nashabeh, F. Hoffmann-La Roche Ltd., Switzerland Peter Richardson, European Medicines Agency (EMA), United Kingdom Anthony Ridgway, Health Canada, Canada The following questions will guide the panel discussion:

1) In recognition of the amount of resources spent pursuing and chasing down technically meaningless regulatory requirements for post-approval change, can we distill down further the changes that really matter to patients?

2) ICH countries are one part of the overall challenge associated with lifecycle management. How can we as an industry work globally to ensure acceptance of pathways such as protocols and established conditions?

3) Protocols are an established and effective mechanism for making change in the US and EU. What opportunities can we as an industry pursue to expand these concepts to ensure more effective and meaningful change submissions?

4) There is a logical connection between the concepts of ICH Q12 and those in ICH Q8, Q9, Q10, and Q11. How will ICH Q12 attempt to bring together these concepts?

5) What is the role of lifecycle management plan in the overall construct of ICHQ12? 6) How will legacy products benefit from ICH Q12? What are the challenges for these products?

NOTES:

NOTES:

Changing Lifecycle Management in Practice:

The Reality of ICH Q12 Concepts Session Chairs: Michelle Frazier, AbbVie, Inc. and Joseph Kutza, MedImmune, A member of the AstraZeneca Group The policies and ideas introduced in the morning session are the first step in the industry's evolution toward more effective post-approval change management. However, this is the first step. How the concepts are implemented in practice by industry and received by regulators on a regional level is the next. This session will provide an overview of practical cases of how the ICHQ12 ideas may be implemented by industry in practice. Active dialogue with global regulators on the acceptability of these practical issues will drive toward a true revolution in post-approval change management that truly benefits patients and improves access. NOTES:

Short Bio’s

Jason Hampson Amgen Inc. Jason Hampson is currently director of regulatory affairs CMC for Amgen Inc., Thousand Oaks, CA, where he is responsible for leading a team of RA CMC professionals providing strategic advice & executional delivery on multiple biologics and synthetic molecule programs at all stages of development. Jason has worked for Amgen for over 13 years in a variety of regulatory roles and supporting worldwide regions and territories. Prior to Amgen, Jason worked at a regulatory affairs consultancy for two years and also for approximately five years at Glaxo/GlaxoWellcome. Jason is an associate director of CASSS and is a member of the organizing committee for the CMC Forum Europe. Jason has been actively engaged in professional and trade associations for many years, including EFPIA, EBE, PDA, TOPRA, EUCRAF and RAPS. Jason received his bachelor’s degree in biological sciences from the University of West of England, Bristol, UK and also has a post-graduate diploma in regulatory affairs from the University of Wales, Cardiff, UK. Kowid Ho F. Hoffmann-La Roche Ltd. Kowid Ho has been working at F. Hoffmann-La Roche Ltd.’s global pharma technical (CMC) regulatory policy group in Basel, Switzerland for two years. He was previously a quality assessor for biological products at Agence nationale de sécurité du médicament et des produits santé (ANSM, formely AFSSaPS) for more than ten years. He has authored many European assessment reports and scientific advices on biotech, vaccines, blood and advanced therapy products, and has participated in several product related inspections. He was a member of European Medicines Agency (EMA) Biologics Working Party (BWP), Biosimilar Working Party (BMWP), PAT team and BWP QbD core group. He was rapporteur for several quality guidelines for EMA (process validation for biological, biosimilar quality aspects, monoclonal antibody). He also participated in the drafting of other European and International guidelines (EDQM HCP general chapter, ICH Q11, revision of WHO guideline for product prepared from rDNA technology). Suzanne Murray Biogen (representing Biophorum Operations Group (BPOG, United Kingdom) Sue Murray is a director of regulatory affairs, CMC at Biogen based in Cambridge, MA. Sue has been at Biogen for 15 years and is responsible for global regulatory CMC strategy for late stage and clinical biological products. She manages a regulatory team responsible for the development of CMC marketing applications, post-approval, and clinical filings. Sue is an active member in industry groups and will represent the Biophorum Operations Group (BPOG) during the CMC Strategy Forum. Sue holds a BS and MS in chemical engineering from the University of Massachusetts, Lowell.

Short Bio’s continued

Anders Vinther Sanofi Pasteur Anders Vinther is chief quality officer at the vaccine company Sanofi Pasteur. He has a MSc and PhD in chemical engineering from the Technical University of Denmark. Anders has worked in many different cultures and has experience from both small and large companies. He was the co-founder of the contract manufacturing organization CMC Biologics, VP of quality in Novo Nordisk, and most recently before joining Sanofi Pasteur he was VP of quality for Genentech and Roche Biologics product operations. Anders is the past chairman of Parenteral Drug Association (PDA), and is a quality thought leader currently working on the Living Quality Ecosystem as well as ways to achieve sustainable quality. Outside his work in the pharma industry Anders is the owner and winemaker at Flying Suitcase Wines. Gresham Weatherly AbbVie, Inc. Gresham Weatherly received his PhD in chemistry from the University of North Carolina studying protein-protein interactions. After graduate school, he worked for a contract biologic manufacturer doing downstream process development and manufacturing support for early phase clinical products. He then moved to Worcester, MA to work for Abbott continuing to work on downstream process development/manufacturing support for biological products. After ten years of process development, Gresham transferred to CMC Regulatory Affairs in Abbott working on biologic products including filing post-approval changes for Humira.

Presenter’s Abstracts

An Industry Perspective: The Complexity of Post-approval CMC Changes and Proposed Regulatory Strategies Suzanne Murray Biogen (representing Biophorum Operations Group (BPOG), United Kingdom Pharmaceutical products save or improve the lives of millions of people throughout the world each year. While thorough regulatory review of Chemistry, Manufacturing and Controls (CMC) information is critical to ensure the safety, quality and efficacy, patients’ quick access to the products is hindered by lack of collaboration among regulators, lack of harmonization in the requirements and extensive review times. Companies race to launch products to patients as soon as possible after clinical efficacy is demonstrated and often, changes such as increased batch sizes and new manufacturing facilities are needed to expand patient access. Additional changes are often made to improve product quality or process robustness as companies gain experience in commercial manufacture. There is tremendous variability in review and approval times for changes in each market, with some markets taking more than 4 years while others approve in a month. Over the course of 4 years, while one country may only approve a single change, another country may approve two dozen. The same core data and information may be reviewed over and over again by approximately 140 individual regulatory bodies according to 140 separate timelines, which dramatically increases the potential for errors in regulatory compliance, complexity in managing inventory, manufacturing costs and risk of interruptions of the product supply to patients. Alternate regulatory strategies are proposed to enable quicker review, approval, and implementation times so that patients can have fast access to high quality products manufactured at the lowest possible costs. NOTES:

Complexities of CMC Change Management & Q12 Opportunities Jason Hampson Amgen Inc., Thousand Oaks, CA USA Throughout the commercial lifecycle, Biopharmaceutical companies need to implement hundreds of Manufacturing and Quality Control changes per year, to ensure an efficient and reliable supply of high quality products. Most changes are managed within the GMP Quality Management System and not subject to reporting to regulatory authorities prior to implementation. Nevertheless the small percentage of reportable changes require significant investment of resources from Industry to manage implementation in a compliant manner without interruption of supply. This presentation will describe some of the strategies employed by companies to manage this complexity, and review some of the opportunities and potential challenges associated with ICH Q12. NOTES:

Improving Post-approval Change processes as a Way to Ensure Technical Innovation and Drug Product Availability Anders Vinther Sanofi Pasteur, Swiftwater, PA USA The ICH Q10 objective of continual improvement including innovation seems to be happening at a slower pace than what many companies would prefer for various reasons. Variations in regulatory processes vary between various countries in terms of requirements and timelines, which leads to a logistics challenge for companies having to manage several product versions at the same time. This is turn increases risk to product availability. If we continue and expand the dialog between industry and regulators we have an opportunity to facilitate more innovation and improve drug product availability. The solution includes reduced regulatory filing submission burden and a strong science and risk based approach to post approval changes. NOTES:

Managing the Product Lifecycle Continuum through Post-approval Change Management Plans: An Industry Perspective Gresham Weatherly AbbVie, Inc., North Chicago, IL USA Managing post-approval changes for globally approved products is cumbersome and can take several years to receive approval globally. While a change is being submitted and reviewed by many regulatory agencies, other changes continue to be evaluated that results in several staggered changes being managed through global approvals. This complexity is difficult to manage, may limit innovation, or result in different product supply chains per market. The use of change management plans can reduce the regulatory complexity and give certainty to change protocols and timelines in ICH markets. However, most of the regulatory complexity and uncertainty is from non-ICH countries. An ideal state for lifecycle management would have change plans approved in global marketing authorizations that would allow change management be conducted within the Quality system, and if required, submitted after implementation. NOTES: Slides were not available at the time of printing.

NOTES:

Changing Lifecycle Management in Practice:

The Reality of ICH Q12 Concepts Workshop Session Two

Panel Discussion – Questions and Answers Jason Hampson, Amgen Inc., USA Kowid Ho, F. Hoffmann-La Roche Ltd., Switzerland Suzanne Murray, Biogen (representing Biophorum Operations Group (BPOG, United Kingdom) Anders Vinther, Sanofi Pasteur, USA Gresham Weatherly, AbbVie, Inc., USA The following questions will guide the panel discussion:

1) Are we going far enough with these examples? Are there opportunities we are missing? 2) Is there an opportunity to standardize approaches across classes of molecules such that we can

push towards more global efficiency? 3) What elements of ICH Q12 do we already do globally? As an example, post-approval stability

protocols are accepted globally even though there isn't an official 'protocol' in the submission. 4) What aspects of ICH Q12 are not practical given business objectives and the reality of post-

approval change? 5) Where should established conditions and non-established conditions live within the dossier

(CTD/QoS)?) or company documentation? 6) How will inspections change during the implementation of ICH Q12?

NOTES:

NOTES: